The Effect of NADP+ on Cardiomyocyte Electrophysiological Properties of C57BL/6 and mdx Mice

摘要

We have studied the influence of NADP+ on routine electrocardiography (ECG) in 6-month-old C57BL/6 and mdx mice. The animals were anesthetized by ether before ECG recording. ECG registration was carried out at a speed of 100 mm/s. The first ECG recording was made before intraperitoneal NADP+ injection in a dose of 13 or 80 mg/kg. The second ECG recording was made 10 min after NADP+ injection. Anesthesia was then terminated. The mice were occasionally anesthetized 45-60 min later, and the third ECG was recorded 1 h after injection of NADP+. ECG recording was carried out at a speed of 100 mm/s in standard leads I, II, and III and unipolar leads AvR, AvL, and AvF. Values of standard ECG characteristics, such as the P wave and the intervals PQ, QT, RR,and the QRS complex, were measured in milliseconds in standard lead II. We did not observe any differences between ECG magnitudes of 2- to 3-month-old C57BL/6 and mdx mice during trial experiments. Mice of both strains had a sinus rhythm in their heart rate. The QRS complex in mdx mice had a tendency to be larger than in C57BL/6 mice. Heart rates fluctuated between 722 ± 22 and 681 ±21 beats per minute. The effect of NADP~+ was studied in 6-month-old male mice. The increase in the RR interval and thedecline in heart rate from 697 ± 21 to 461 + 23 and 491 ± 28 beats per min for C57BL/6 mice (p < 0.01) and from 722 ± 28 beats per minute to 454 ± 31 beats per min for mdx mice were registered 10 min after NADP~+ injection at a dose of 80 mg/kg. Theincrease in the RR interval can be explained by an increase in the QT interval. A statistically significant reduction in the QT interval leading to a diminished RR interval was observed in mdx mice 1 h after NADP~+ injection. NADP~+ at a dose of 13 mg/kgdid not significantly change the ECG properties in mdx mice. ECG of mdx mice was characterized by negative repolarization of the T wave in 37% of all leads. The amount of leads with negative T-wave repolarization decreased up to 3% 1 h after NADP~+ injection in dose of 80 mg/kg. The results have shown that cytomembranes of ventricular cardiac myocytes and the degree of oxidative stress are the main targets of the action of NADP~+ in C57BL/6 and mdx mouse hearts.